This project will investigate the relationship between the activities of human plasma lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein in regulating efflux of cholesterol from cultured cells, and the activity of cellular receptors mediating lipoprotein endocytosis and interiorization of lipoprotein cholesteryl ester. In this way, information on sterol balance between plasma and cells will be provided. Cell models will include major cell species of the vascular bed (endothelial and smooth muscle cells and macrophages) as well as fibroblasts. LCAT is known to be linked structurally and kinetically to transfer protein activity in normal human plasma (Fielding and Fielding, Proc. Nat. Acad. Sci. USA 77:3327, 1980). In this project, the structure and functions of the transfer complex will also be investigated in well-defined human hypercholesterolemic syndromes.